Pregnancy increases maternal ventilation. At high altitude where O2 availability is reduced and fetal growth retarded, increased ventilation raises arterial O2 saturation and may influence maternal well-being and fetal growth. The proposed research aims to determine the mechanisms by which maternal hypoxic ventilatory response is increased with pregnancy, the locus of pregnancy's effects, and the contribution of increased hypoxic responsiveness to the increased ventilation of pregnancy. We hypothesize that maternal ventilatory response to hypoxia increases with pregnancy as a result of increased progestin levels, progesterone receptor numbers, and metabolic rate. Studies will be carried out in human beings to determine the effect of increased progestin levels, progesterone receptor numbers, and metabolic rate on hypoxic ventilatory response; the influence of gender on these modulators of hypoxic responsiveness; and the contribution of the increased hypoxic ventilatory response to the increased maternal ventilation of pregnancy. Studies of carotid body and respiratory output in cats will seek to determine the locus at which pregnancy influences hypoxic ventilatory response. The studies may be important for understanding the changes that normally occur with pregnancy and the reasons why some women raise their ventilation and deliver larger babies at high altitude than others. They may also be important for understanding gender differences and hormonal influences on ventilatory control and contribute to the long-term objective of identifying the influence of maternal ventilation on O2 transport, maternal and fetal well-being and the process by which adaptation to high altitude may occur.